Nanotechnology based signal amplification for biosensing has been investigated over the last decade. Several categories of nanomaterials such as gold nanoparticles, magnetic oxide nanoparticles, carbon nanostructures, and semiconductor nanoparticles have seen a multitude of applications in this aspect due to their unique physical or chemical properties. For instance, gold nanoparticles have been used as substrates for surface enhanced Raman scattering (SERS) or fluorescence due to the intensified local electromagnetic fields on their surfaces. Magnetic oxide nanoparticles have been employed as signal enhancers or amplifiers in surface Plasmon resonance (SPR) or quartz crystal microbalance (QCM) biosensors due to their high refractive index and molecular weight. Carbon nanotubes and graphene oxide have been adopted as biolabels to carry more enzymes for signal amplification due to their long length or large surface area. Semiconductor nanoparticles (quantum dots) have brighter fluorescence than conventional organic fluorophores and thus have replaced organic fluorophores in various bioassays. In addition, because semiconductor nanoparticles are chemically composed of heavy metal ions such as Cd2+, they also can release hundreds of thousands of heavy metal ions (this metal ion release is considered to be a signal amplification process). The released metal ions can be deposited on a mercury electrode for electrochemical detection, or they can bind with non-fluorescent, metal-ion sensitive dyes to generate fluorescence for signal measurement.
Most of the aforementioned approaches are single-stage signal amplification processes. Recently, several works have introduced dual signal amplification by coupling two single signal enhancement approaches in signal transduction of biosensing. Dual signal amplification is anticipated to be more efficient at improving bioassay sensitivity or lowering detection limits, because it has a higher signal gain. However, the reported dual signal amplification strategies mainly focus on applying carbon nanomaterials or gold nanoparticles. For example, some electrochemical bioassays applied carbon nanotube or graphene to not only increase sensing areas but also carry more labeling enzymes. Gold nanoparticle-based bio-barcode assays utilized gold nanoparticles to load more barcode DNA labels and additionally to catalyze silver enhancement for the detection of biomolecules.
Many of the presently available amplification processes whether signal—stage or dual-stage are inadequate. For example, many are labor intensive, have insufficient sensitivity, or utilize reagents that can be harmful to the environment. Therefore, more sensitive, cost-efficient, less toxic bioassays are needed.